RESUMO
INTRODUCTION AND OBJECTIVES: Ubiquitin-specific proteases (USPs) act as proto-oncogenes or tumor suppressors in a wide variety of cancers. In this study, we intended to explore the role of USP1 in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The clinical significance of USP1 in HCC was analyzed based on The Cancer Genome Atlas (TCGA) data and immunohistochemical staining. siRNAs and lentivirus were used to knock down and overexpress indicated genes, respectively. qRT-PCR and immunoblotting were performed to examine mRNA and protein expression, respectively. CCK8, colony formation and PI/Annexin V-APC staining were performed to examine cellular function. Immunoprecipitation, coomassie blue staining, mass spectrum and immunoblotting were conducted to evaluate the interaction between USP1 and c-kit. RESULTS: USP1 was over-expressed in HCC patients. Patients with high expression of USP1 had shorter overall and disease free survival than those with low expression of USP1. Functional results showed that USP1 was critical for HCC cell growth and proliferation. Immunoprecipitation and immunoblotting results suggested that USP1 interacted with c-kit and promoted the stability of c-kit, which is an important target of lenvatinib in HCC. Knockdown of c-kit reversed the oncogenic function of USP1 on HCC cell growth. Lastly, USP1 upregulation conferred higher sensitivity of HCC cells to lenvatinib treatment. CONCLUSIONS: Our study demonstrated that USP1 acted as an oncogene in HCC. It also promoted lenvatinib efficacy by stabilizing c-kit.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Oncogenes , Compostos de Fenilureia , Quinolinas , Receptores Proteína Tirosina Quinases/genética , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismoRESUMO
Hepatocellular carcinoma (HCC) has a high dead rate partly due to late diagnosis. This study aimed to investigate the prognostic value of miR-937 in HCC and its role in the HCC progression. HCC tissue and adjacent non-cancerous tissues (NCT) (n = 125) were detected about the expression level of miR-937 via real-time quantitative PCR. The relationship between miR-937 expression and each important clinical characteristic was evaluated. And the prognostic significance of miR-937 was assessed by Kaplan-Meier curve and Cox regression analysis. CCK-8 and Transwell assays were conducted to observe the effects of miR-937 on HCC cell proliferation, migration, and invasion. The miR-937 expression was upregulated in HCC tissues, as well as in HCC cell lines. The upregulation of miR-937 showed a significant association with lymph node metastasis and TNM stage. Upregulation of miR-937 predicted poor prognosis of HCC patients. Overexpression of miR-937 promoted HCC cell ability of proliferation, migration, and invasiveness, while knockdown of miR-937 inhibited these cellular behaviors. miR-937 expression was upregulated in HCC and may serve as a promising prognostic factor and treated target for HCC patients. miR-937 might exert a promoter role in HCC through accelerated tumor cell proliferation, migration, and invasion.
